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Mitochondrial DNA Damage: Prevalence, Biological Consequence, and Emerging Pathways.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-06-03 , DOI: 10.1021/acs.chemrestox.0c00083
Linlin Zhao 1 , Philip Sumberaz 1
Affiliation  

Mitochondria have a plethora of functions within a eukaryotic cell, ranging from energy production, cell signaling, and protein cofactor synthesis to various aspects of metabolism. Mitochondrial dysfunction is known to cause over 200 named disorders and has been implicated in many human diseases and aging. Mitochondria have their own genetic material, mitochondrial DNA (mtDNA), which encodes 13 protein subunits in the oxidative phosphorylation system and a full set of transfer and rRNAs. Although more than 99% of the proteins in mitochondria are nuclear DNA (nDNA)-encoded, the integrity of mtDNA is critical for mitochondrial functions, as evidenced by mitochondrial diseases sourced from mtDNA mutations and depletions and the vital role of fragmented mtDNA molecules in cell signaling pathways. Previous research has shown that mtDNA is an important target of genotoxic assaults by a variety of chemical and physical factors. This Perspective discusses the prevalence of mtDNA damage by comparing the abundance of lesions in mDNA and nDNA and summarizes current knowledge on the biological pathways to cope with mtDNA damage, including mtDNA repair, mtDNA degradation, and mitochondrial fission and fusion. Also, emerging roles of mtDNA damage in mutagenesis and immune responses are reviewed.

中文翻译:

线粒体 DNA 损伤:流行、生物学后果和新兴途径。

线粒体在真核细胞内具有多种功能,从能量产生、细胞信号传导和蛋白质辅因子合成到代谢的各个方面。众所周知,线粒体功能障碍会导致 200 多种疾病,并与许多人类疾病和衰老有关。线粒体有自己的遗传物质,即线粒体 DNA (mtDNA),它编码氧化磷酸化系统中的 13 个蛋白质亚基以及全套的转移和 rRNA。尽管线粒体中超过 99% 的蛋白质是核 DNA (nDNA) 编码的,但 mtDNA 的完整性对线粒体功能至关重要,由 mtDNA 突变和耗竭引起的线粒体疾病以及碎片化的 mtDNA 分子在细胞中的重要作用证明了这一点。信号通路。先前的研究表明,mtDNA 是受到各种化学和物理因素影响的基因毒性攻击的重要目标。本视角通过比较 mDNA 和 nDNA 中病变的丰度来讨论 mtDNA 损伤的普遍性,并总结了应对 mtDNA 损伤的生物学途径的当前知识,包括 mtDNA 修复、mtDNA 降解以及线粒体裂变和融合。此外,还审查了 mtDNA 损伤在诱变和免疫反应中的新作用。
更新日期:2020-06-03
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